A new approach to study the genetics of behavior and the nervous system in Drosophila is proposed. Our objective is to isolate mutations which lead to altered, or an absence of, activity of the nervous system enzyme acetylcholinesterase (AChE). Preliminary results on biochemical and histochemical assays of this enzyme are described, which indicate the excellent potential for monitoring the activity of the enzyme in the nervous system. Moreover, we present genetic results on a successful search for a chromosome region which controls acetylcholinesterase activity; the current genetics of the system maximizes the chances of isolating mutations in the AChE-controlling gene. We propose to isolate temperature-sensitive AChE-null mutations. We plan to use the mutations (1) as axonal markers, in genetic mosaics for which some parts of the nervous system lack AChE activity, (2) in studies of the functioning of different parts of the nervous system, which can be turned off in mosaics carrying the temperature-sensitive null allele, (3) in studies of transmitter metabolism in different parts of the nervous system, (4) in studies of the effects of this enzyme on the developing animal. An AChE genetic system would prove very useful in analyzing the effects on behavior of other neurological mutations in Drosophila, and in analyzing the control exerted on behavior by different regions of the major ganglia in the fly.